CN101896140B

CN101896140B - Devices and methods for treating spinal cord tissue

Info

Publication number: CN101896140B
Application number: CN200880121075.8A
Authority: CN
Inventors: L·C·阿金塔; D·L·凯罗; N·H·利瓦伊; 刘杰; M·J·莫里夸斯; S·塔特; W·D·沃纳
Original assignee: Wake Forest University Health Sciences
Current assignee: Wake Forest University Health Sciences
Priority date: 2007-10-10
Filing date: 2008-10-09
Publication date: 2014-01-08
Anticipated expiration: 2028-10-09
Also published as: US20200384168A1; BRPI0817544A2; ZA201002498B; US20090187259A1; KR20100100798A; RU2010118021A; JP2011500163A; JP5462175B2; CA2702239A1; IL204825A0; EP2205189A1; AU2008310819A1; AU2008310819B2; ES2661762T3; US8834520B2; CA2702239C; US20170368242A1; WO2009049058A1; US10632235B2; RU2489993C2

Abstract

The present invention provides devices and methods that treat damaged spinal cord tissue, such as spinal tissue damaged by disease, infection, or trauma, which may lead to the presence of swelling, compression, and compromised blood flow secondary to interstitial edema.

Description

The apparatus and method that are used for the treatment of myeloid tissue

Invention field

The present invention relates generally to the apparatus and method of the myeloid tissue that adopts negative pressure treatment damage or infringement, and more particularly, but be not exclusively, relate to being used for the treatment of to experience and can recover or the apparatus and method of the myeloid tissue of irrecoverability damage.

Background of invention

The treatment of the myeloid tissue that relates to anatomy, physiology and the pathological process special concern damage of spinal cord attitude or damage.The three dimensional structure anatomy of neuroprotective unit (its function depends on the special space relation with other neuron and other sustenticular cell) concern both with microanatomy and maintain suitable oxygen enrichment blood flow and wherein the homogeneous phase substrate of neuronal survival be myeloid tissue survive and function necessary.In addition, cord cell can not be regenerated and given prominence to for making each possible neuronic survival reach demand to greatest extent.Due to for example these reasons, the space sickness Neo-Confucianism for the treatment of spinal cord attitude open and closed system is the problem of special concern.

In the clinical problem that threatens myeloid tissue's survival is arranged, it is main controlling edema of spinal cord, infection and blood supply.Spinal cord responds to wound and damage by the interstitial edema of collecting significant quantity.Because spinal cord is closed in the space (dura mater and ridge pipe) of sealing, the blood flow that edema causes spinal cord is with the compression of performance nutrition and weaken, and this physiology that damages widely spinal cord recovers and usually therefore cause the development and death of spinal cord lesion.Comprise medicine for reducing the current available treatment of edema, for example glucocorticoid (dexamethasone, prednisone, methylprednisolone), diuretic and decompression widely.Yet, for the unfavorable conditions of these treatments, comprise irregular and unpredictable results, medicine complication, infection and postoperative complication.

Due to disastrous consequence and the high likelihood of spinal cord infection with the fast propagation of edema, to demand quick and that effectively treat, be also extremely important.There is at present the successful methods of the pathological changes of several available treatment invasion and attack spinal column inner chambers, spinal cord essence and surrounding structure.When organizing of health other places is available, change dressings while processing, spinal cord is because its unsettled structure, the potentiality that infect tendency and lesion development are not suitable for the type treatment.Illustrate on evidence the inflammation of spinal cord injury and other pathological changes and immunne response are had with initial damage or injure identical or than initial damage or the more long-term consequence of injury.Spinal cord causes the damage of hypoxia and the mediation of local ischemia/reperfusion to replying of the Oligemia that is secondary to edema.These damages cause neuro pathology's sequela, and the latter causes again the unfavorable result of spinal cord injury to a great extent.

In addition, spinal cord need to continuously be supplied with the oxygen enrichment blood flow with performance function and survival.Interrupting blood flow to spinal cord fully in a few minutes, cause irreversible spinal cord injury.Yet, spinal cord can survive and the blood flow that certainly reduces in recover the period more extended.The focus zone (focal areas) that spinal cord is described on evidence can keep ischemia with relative nonfunctional a couple of days and still can recover.This discovery has caused the concept in ischemia zone, is called penumbra Huo Yun district (halo zone), and it is around the zone of irreversible damage.The secondary phenomenon in ischemia zone (secondary phenomena) is to discharge by the local excitatory neuron toxin discharged of the neuron of damage, variation and the edema of focal zone blood flow.

The angiological pathology of spinal column can be following result: because perfusion pressure reduces, cause the angiorrhexis to local spinal cord zone coup injury, or make to flow to the hematopenia of cord cell by compressing adjacent tissue; Such as atherosclerosis, aneurysm, inflammation etc. of spinovascular intrinsic disease; From other places for example heart be deposited on the sparse thrombosis in the spinal cord blood vessel.

In the situation that the spinal column internal hemorrhage, the hemorrhage fritter material usually used as dissect the volume growth of (pressure dissection) with pressure starts and causes the myeloid tissue of displacement and compressing vicinity.Edema in the hemorrhage oppressed tissue of vicinity on every side can cause by the more large-area myeloid tissue of infringement the deterioration of mass effect and clinical condition.Edema in contiguous spinal cord can cause usually through the deterioration of 12-72 hour visible carrying out property.Edema occurs in one week after the spinal column internal hemorrhage and usually make prognosis become even worse, especially in aging people.Perihematoma organize replaced and compressing, but not necessarily fatal infringement.Improvement can be absorbed due to hematoma again, contiguous decrease in edema and the organized renewing function of getting involved obtain.

Treat these diseases and made people's disappointment.It may be useful that the decompression of spinal cord prevents in the case of irreversible compressing at some.Reagent for example other penetrating agent of mannitol and some can reduce the spinal column internal pressure caused by edema.Steroid has uncertain value in these cases and current built view adopts hyperbaric oxygen.

Therefore, although to injured skin and subcutaneous tissue apply negative pressure (or negative pressure) therapy confirm with traditional method relatively Healing Rate increase and (set forth in No. the 2003/0225347th, 2004/0039391 and 2004/0122434, No. the 5645081st, 5636643,7198046 and 7216651, US patent and the disclosed application of US, its content is attached to herein by reference), still need to be specially adapted to the apparatus and method of special myeloid tissue.

Summary of the invention

The invention provides the myeloid tissue that adopts negative pressure (or negative pressure) treatment damage, for example, by the apparatus and method of the myeloid tissue of disease, infection or wound infringement, described disease, infection or wound can cause being secondary to the existence of blood flow of swelling, compressing and the minimizing of interstitial edema.For example, spinal cord can be by causing recovering or the blunt force injury damage of expendable damage.

In one aspect, the invention provides the method for the myeloid tissue that adopts the negative pressure treatment damage.The method comprises porous material is placed in to approach between the myeloid tissue of myeloid tissue with the one or more holes at porous material and damage of damaging provides gas communication (gaseouscommunication).Porous material can be sealed in the myeloid tissue that approaches damage on the spot, so that the zone of the myeloid tissue's maintenance negative pressure that maintains damage to be provided around the myeloid tissue in damage.Porous material can be connected by the vacuum system that operationally with myeloid tissue in damage, produces negative pressure, and the vacuum system started provides negative pressure in the myeloid tissue of damage.Can in the myeloid tissue of damage, keep negative pressure to be enough to reduce at spinal cord the time of edema.For example, negative pressure can remain on lower than the about 25mm Hg of atmospheric pressure.The method also can be included in the myeloid tissue of damage settles protective layer seal protection layer in the tissue of the myeloid tissue that approaches damage, for the myeloid tissue in damage, keeps negative pressure.The form that protective layer can be placed in the autoadhesion sheet (self-adhesive sheet) in the myeloid tissue of damage provides.In such a case, the step of seal protection layer can comprise and seal deadlockedly and make the autoadhesion sheet adhere to the tissue around the Spinal Cord tissue, between described and tissue around the myeloid tissue of damage, to form sealing.

In yet another aspect, the invention provides the device that is used for the treatment of the Spinal Cord tissue.But this device can comprise the biology bond material of porous for example opens chamber (open-cell) collagen protein, it has the pore structure that is shaped to allow carry out gas communication between one or more holes of porous material and the myeloid tissue for the treatment of.The biological combinableness matter of porous material can avoid needing second method to remove porous material.(as used herein term " biological combinative " be defined as describing can be positioned over for a long time in patient body and can be by refigure, the material reuptaking, dissolve and/or otherwise assimilate or modify).Device also comprises the vacuum source for generation of negative pressure; Vacuum source can be configured for the distribution negative pressure to myeloid tissue with the mode of the gas communication of porous material.Porous material at least can have on the surface of the selection of porous material enough little hole to prevent from being organized in wherein growth.In addition, porous material at least can have the pore size that is less than fibroblast and cord cell size on the surface of the selection of porous material, and can have in the position except selected surface the pore size that is greater than fibroblast and cord cell size.The pore size of porous material can be even as big as the protein motion that allows the albumin size to pass through.And, but the biology bond material of porous can comprise at least one sealed surface to prevent that negative pressure from therefrom transmitting.Device also can comprise the protective layer in the myeloid tissue that is shaped to cover damage, under the protective layer at the Spinal Cord tissue, to keep negative pressure.

Therefore, the progress the invention provides for making pathological process reduces to minimum, makes the destruction of physiology spinal cord integrity reduce to minimum and make the interference of spinal cord blood flow and nutrition is reduced to minimum apparatus and method.By reducing edema of spinal cord and spinal column internal pressure, the risk that spinal cord forms hernia and infringement can be reduced to minimum.In addition, the present invention is convenient to remove the toxin that in medium, catabolite and enhancing spinal cord, the neuro pathology of inflammation and tissue replys.

The accompanying drawing summary

When read in conjunction with the accompanying drawings, above-mentioned general introduction and the following detailed description of the preferred embodiments of the invention will get the best understanding, wherein:

Fig. 1 illustrates the partial sectional view of the example arrangement of apparatus of the present invention before applying negative pressure on the spot;

Fig. 2 illustrates the partial sectional view of Fig. 1 when applying negative pressure;

Fig. 3 illustrates and is presented at the partial sectional view of Fig. 1 and 2 that the spinal cord surrounding tissue applies the effect of negative pressure;

Fig. 4 illustrates and comprises on the spot the subcutaneous partial sectional view that is configured in second example arrangement of the present invention of epispinal rigidity or semi-rigid protective layer;

Fig. 5 illustrates and comprises on the spot the subcutaneous partial sectional view that is configured in the 3rd example arrangement of the present invention of epispinal flexible protective layer;

Fig. 6 for example understands that the BBB scoring is as the time function that is exposed to the control animal of recoverable spinal cord blunt wound;

Fig. 7 for example understands the time function of BBB scoring as the animal that is exposed to recoverable spinal cord blunt wound and processes by negative pressure;

Fig. 8 for example understands the spinal cord sectional area as the time function of the control animal that is exposed to expendable spinal cord blunt wound;

Fig. 9 for example understands the spinal cord sectional area as the time function of the animal that is exposed to expendable spinal cord blunt wound and processes by negative pressure; With

Figure 10 illustrates the porous material had for the multiple structure of negative pressure device of the present invention.

Detailed Description Of The Invention

While mentioning accompanying drawing now, wherein same parts adopt identical numbering in the text, the present invention relates to adopt the apparatus and method of the myeloid tissue of negative pressure (or negative pressure) treatment damage, wherein " damage " tissue be defined as comprising be damaged, damage or with any alternate manner weakening for example due to the tissue of wound, disease, infection, postoperative complication or the damage that for example other pathological process causes.More particularly, apparatus and method of the present invention can realize more than any reason for example mentioning the treatment of the Secondary cases spinal cord essence edema of reason; Around spinal cord, any gap comprises the treatment of subdural space/epidural space; With the treatment raise due to any reason spinal column internal pressure that for example above-mentioned reason causes.

The example arrangement of negative pressure medullotherapy device 100 of the present invention can comprise for the vacuum source 30 of negative pressure, Fig. 1-3 are provided to the porous material 10 that is arranged in contiguous spinal cord 7 by pipeline 20.In this respect, can construct porous material 10 to transmit and the distribution negative pressure to spinal cord 7.Medullotherapy device 100 can be applied to the patient by the myeloid tissue 7 that porous material 10 is placed in to contiguous damage, between the myeloid tissue 7 with the one or more holes at porous material 10 and damage, provides gas communication.Pipeline 20 can be connected in porous material 10 at the far-end 22 of pipeline 20, and porous material 10 can seal on the spot by the stitching thread 8 in skin and subcutaneous tissue 2, around the myeloid tissue 7 in damage, to provide a zone for keeping negative pressure.The near-end 24 of pipeline 20 can be connected to vacuum source 30 with porous material 10 and the vacuum source 30 of being operably connected, and for the myeloid tissue 7 in damage when starting vacuum system 30, produces negative pressure.

Forward more detailed Fig. 1 to, patient's surrounding tissue that the example arrangement of negative pressure medullotherapy device 100 of the present invention shows at partial sectional view is illustrated on the spot.The tissue of example explanation comprises skin and subcutaneous tissue 2, muscular tissue for example trapezius muscle 3 and erector spinae 4, vertebra 5, transverse process 6 and spinal cord 7.To lead to spinal cord 7 in order providing, can to lack a part of vertebra 5.For example, spinous process can lack due to operation dissection, disease or damage.Porous material 10 is for example opened the subcutaneous space that the chamber collagen material for example can be placed in the contiguous myeloid tissue 7 with negative pressure treatment, with the edema that reduces parenchymal tissue with improve physiological function.Except opening the chamber collagen material, porous material 10 also can comprise polyglycolic acid and/or poly-lactic acid material, synthetic polymer, flexible sheets sample sieve aperture, open the chamber foam of polymers, foam segment, porous chips, polyvinyl alcohol foam, polyethylene and/or polyester material, elastin laminin, hyaluronic acid, alginate, polyglycols citron acid esters, poly butyric ester, poly-hydroxyfumaric acid ester, PTMC, polyglycereol sebacate (sebecate), the poly-anhydride of aliphatic/aromatics or other suitable material, and for example can pass through electrospinning (electropinning), the combination of any above-mentioned material of casting or printing preparation.Such material comprises chitosan solution (1.33% weight/volume in 2% acetic acid, 20ml cumulative volume), and it can be poured in the mould of suitable size.Then make solution under-70 ℃ freezing 2 hours, then be transferred in lyophil apparatus and apply vacuum 24 hours.Described material can, by 2.5%-5% glutaraldehyde steam crosslinked 12-24 hour (or passing through ultraviolet radiation 8 hours), provide casting porous material 10.

In addition, porous material 10 can be by casting polycaprolactone (PCL) preparation.The chloroform that polycaprolactone can mix with sodium chloride (1 part of caprolactone is to 10 parts of sodium chloride) and be placed in enough volumes is with dissolved constituent.For example, the solution of 8ml can be poured in the container of suitable size and shape and make it dry 12 hours.Then can make sodium chloride leach in water 24 hours.

Also can use the electrospinning material for porous material 10.It for the preparation of the preparation of electrospinning porous material 10 and an illustration of method, is the Collagen type I adopted with the ratio existence of 76%: 4%: 20% (weight): ch.-6-s (CS): the combination of poly-1,8-ethohexadiol citron acid esters (POC).Two kinds of solvents are for collagen/CS/POC.Make CS soluble in water and collagen and POC are dissolved in 2,2,2-trifluoroethanol (TFE).Then use the solution of 20% water/80%TFE solution (volume/volume).For electrospinning, will contain collagen: CS: the solution of POC mixture is placed in the 3ml syringe that is equipped with the 18Ga pin.Syringe pump (New Era Pump Systems, Wantaugh, NY) is for being delivered to the pin end by solution with the speed of 2.0ml/hr.10-20kV voltage is provided and is applied to distance between the pin of 15-25cm (anode) and ground connection catcher (negative electrode) through high voltage power supply (HV PowerSupply, Gamma High Voltage Research, Ormond Beach.FL).Then make the crosslinked and thermal polymerization (80 ℃) of this material and glutaraldehyde (II level, 25% solution) 48 hours.Also can the initial concentration in HFIP (HFP) be 80mg/ml collagen starts electrospinning Collagen type I porous material 10, then adopt and combine identical electrospinning condition with collagen: CS: POC.

A kind of other method for generation of porous material 10 is to adopt the thermal inkjet-printing technology.But biology bond material for example collagen, elastomer, hyaluronic acid, alginate and polylactic acid/polyglycolic acid copolymer can be printed.For example, be dissolved in 0.05% acetic acid, then be diluted with water to type i collagen (the Elastin Products Co. of 1mg/ml, Owensville, MO) can be printed, as sodium alginate (Dharma Trading Co., San Raphael, CA) 1mg/ml is printable the same in water.Type i collagen (2.86mg/ml is in 0.05% acetic acid) and polylactic acid/polyglycolic acid (PURAC America, Blair, NE) (14.29mg/ml is (SigmaAldrich, St.Louis MO) in tetraethylene glycol (TEG)) also can be printed.Comprise motor and can be installed in platform for the spool bed (carriage) of ink powder tube (cartridges) from the hardware of Hewlett Packard 660c printer.Then the height of capable of regulating hardware more than platform printed for layering.

Porous material 10 can comprise enough little hole in the interface between porous material 10 and spinal cord 7, and to prevent from being organized in wherein growth, for example pore size is less than the size of fibroblast and cord cell; Otherwise porous material 10 can adhere to spinal cord 7 and cause bleeding when removing porous material 10 or wound.In addition, the pore size on interface between porous material 10 and spinal cord 7 can be enough little, in order to avoid excessively producing granulation or scar tissue on spinal cord 7, granulation or scar tissue can disturb the physiological function of spinal cord 7.Simultaneously, the pore size of porous material 10 can must be enough to greatly the protein motion that allows the albumin size to pass through, for example, to allow to remove undesirable compound, medium, catabolite and toxin.

For example, yet porous material 10 can or have larger pore size (being greater than the size of fibroblast and cord cell) in any other position of the porous material 10 do not contacted with myeloid tissue 7 in the inside of porous material 10.For example, porous material 110 can comprise the multiple structure with non-inside grown layer (non-ingrowth layer) 112, it has enough little pore size and wherein grows and alternative spinal cord to prevent from being organized in, and can there is the additional layer 114 of different materials, it has the relative larger pore size with non-inside grown layer 112 contacts.

Perhaps, porous material 10 can be uniform aspect composition and/or morphology.Position at the interface away from spinal cord 7, porous material 10 can have the pore size that promotes to form granulation tissue even as big as other tissue in the surrounding space at spinal cord 7, and the zone promotion formation granulation tissue that spinal cord breaks for example occurs.In addition, it is sealed in case stop-pass is crossed the surface transmission negative pressure of such sealing that porous material 10 can have one or more sides or the surface of porous material 10 wherein, and have the structure on the surface that at least one can be by its transmission negative pressure simultaneously.Can there be the tissue of priority treatment in such structure of porous material 10 and process other side in a side of porous material 10.For example, non-tight interface processing when, the essence of spinal cord 7 can be with a side of porous material 10.

Porous material 10 can comprise the material that need to remove after giving negative pressure therapy, and it can need second operation.Perhaps, but porous material 10 for example can comprise elapsed time bio-absorbable or harmless degraded, to avoid the material of second operation, collagen.In addition, porous material 10 can comprise nonmetallic materials, in order to can implement MRI simultaneously porous material 10 on original position.If porous material 10 also can comprise the material of enough compliances so that it compresses spinal cord 7, porous material 10 does not affect spinal function.Simultaneously, porous material 10 can comprise enough solid material, so that porous material 10 does not collapse to the degree that generation can affect stretching or the distortion " normal spinal cord " of spinal function.

In order to porous material 10, to transmit negative pressure to be distributed to spinal cord 7, pipeline 20 can be connected with the mode of porous material 10 with gas communication directly or indirectly at the far-end 22 of pipeline 20.For example, the far-end 22 of pipeline 20 can be embedded in porous material 10 or can be placed on porous material 10.The far-end 22 of pipeline 20 also can comprise one or more perforation to help to porous material 10 and spinal cord 7 transmission negative pressure.Pipeline 20 can extend by the opening in skin and subcutaneous tissue 2, and its available stitching thread 8 provides sealing around being fixed on pipeline 20 around pipeline 20 with help.The near-end 24 of pipeline 20 can be operably connected to vacuum source 30, and vacuum pump for example, to provide the negative pressure to porous material 10 and spinal cord 7 transmission by pipeline 20.

Vacuum source 30 can comprise controller 32 to regulate the generation of negative pressure.For example, vacuum source 30 can be shaped to produce continuously or off and on negative pressure; For example vacuum source 30 can circulate to provide the alternate cycles that produces and do not produce negative pressure by spells.Buty cycle between producing and not producing can be between 1:10 (ON/OFF)-10:1 (ON/OFF).In addition, intermittently negative pressure can through periodicity or cyclicity waveform for example sine wave apply.Vacuum source 30 can be circulated in initial treatment after simulating more physiological status, for example several times per minute.Negative pressure can circulate off and on when needed as the piezometry through monitoring spinal cord 7.Usually, vacuum source 30 can be shaped to transmit negative pressure at atmospheric pressure and between lower than atmospheric pressure 75mm Hg, so that negative pressure can cause hemorrhagely entering spinal cord 7 or opposing that mutually chance that spinal cord 7 is harmful reduces to minimum.Can handle and apply such negative pressure from spinal cord 7, to remove edema, so the neuroprotective function is to increase the probability of more Physiological protection recovering state and survival.

In order to contribute to keep the negative pressure of spinal cord 7, can provide flexible protective layer/sheet 50 or rigidity (or semi-rigid) protective layer 40 approaching spinal cord 7 places, so that a zone that can keep negative pressure, Fig. 4,5 to be provided around spinal cord 7.Specifically, with reference to Figure 4 and 5, the

zone

48,58 of tissue to seal in spinal cord 7 and restriction around porous material 10 that approaches spinal cord 7 by

protective layer

40,50 is adhered to can provide

protective layer

40,50 on spinal cord 7 and porous material 10.For example,

protective layer

40,50 can adopt binding agent 42 for example Fibrin Glue adhered to vertebra 5, muscular tissue 4 and/or other suitable tissue.Binding agent 42 can comprise autohemagglutination rubber alloy (auto-polymerizing glue) and/or can desirably comprise filler, so that the binding agent 42 with enough volumes to be provided, so that binding agent 42 can meet the shape of the potential irregular surface of binding agent 42 contacts.Binding agent 42 can be used as component separately or provides as the part of

protective layer

40,50, so that half gluing

protective layer

40,50 to be provided.For example, protective layer 50 can comprise flexible half sheet adhesive, and it comprises suitable binding agent on its one or more surfaces.

For flexible protective layer 50, the outward flange of flexible protective layer 50 or edge can twist in spinal cord 7 times (or to) spinal cord 7 is rolled.Perhaps, but flexible protective layer 50 rolling off spinal cord 7, so that then following (side is facing to the porous material 10) of protective layer 50 can contact with muscle and soft tissue on every side with vertebra 5, Fig. 5.If flexible protective layer 50 is rolled for 7 times at spinal cord, binding agent 52 can be coated on the outside of the protective layer 50 between protective layer 50 and vertebra 5, muscle and soft tissue on every side so, to help to promote gas-tight seal.If flexible protective layer rolling off spinal cord 7, binding agent can be applied to the following of protective layer 50 between protective layer 50 and vertebra 5 and on every side muscle and soft tissue to produce gas-tight seal.

Negative pressure can the transmission of the cooperation between

protective layer

40,50 and pipeline 20 below protective layer 40,50.Specifically, protective layer 40 (or flexible protective layer 50) can comprise the vacuum valve 43 be connected with the far-end 22 of pipeline 20, so that the gas communication between pipeline 20 and the space 48 above the following spinal cord 7 of protective layer 40, Fig. 7 to be provided.Perhaps, protective layer 50 (or protective layer 40) can comprise the path 52 that pipeline 20 passes through so that the far-end 22 of pipeline 20 is configured in below protective layer 50 in the space 58 above spinal cord 7 and with space 58 gas communications, Fig. 5.

Protective layer

40,50 can be used for further limiting spinal cord 7 subcutaneous area on every side that keeps negative pressure.As graphic extension in Figure 4 and 5;

protective layer

40,50 provides the space of sealing/

zone

48,58 around spinal cord 7 below

protective layer

40,50, and it can be used for separating tissues and is not exposed in the outside of

protective layer

40,50 negative pressure that imposes on spinal cord 7.On the contrary; as graphic extension in Fig. 2 and 3; in unprotected situation; be transferred to porous material 10 and can inwardly towards pipeline 20 and porous material 10, attract surrounding tissue along the direction of arrow shown with the negative pressure of spinal cord 7 in Fig. 2; for example muscle 3,4, cause the organizational structure that diagram shows in Fig. 3.In this respect, stretch and/or moving tissue for example muscle 3,4 can help applied negative pressure is limited to the zone between muscle 4 and spinal cord 7.In addition,

protective layer

40,50 can further protect spinal cord 7 that the exogenous infection that can't protect and the pollution that are provided by porous material 10 and the skin 2 sewed up are provided.Equally,

protective layer

40,50 can further protect surrounding tissue to avoid the infection diffusion that for example spinal cord abscess, meningitis and myeloid tissue infect from spinal cord 7.

Aspect its another, the present invention also provide for by for example at the device of Fig. 1-5 graphic extension, adopt the method for the myeloid tissue of negative pressure treatment damage.Specifically, method can comprise the myeloid tissue 7 that porous material 10 is placed in to approaching damage, between the myeloid tissue 7 with the one or more holes at porous material 10 and damage, provides gas communication.Porous material 10 can be sealed on the spot in the myeloid tissue 7 that approaches damage, with the zone that provides for the myeloid tissue 7 in damage, to keep negative pressure around the myeloid tissue 7 in damage.In this respect, but muscle 3,4 and subcutaneous tissue loosely the top of porous material 10 with by skin 2 with sew up the pipeline 20 that the skin 2 of sealing leaves away and reaccees.The dressing of another gas-tight seal can optionally be placed in suture location to promote gas-tight seal.Porous material 10 can be operably connected to vacuum system 30, for the myeloid tissue 7 in damage, produces negative pressure, and vacuum system 30 is actuated to provide negative pressure in the myeloid tissue 7 of damage.For example, negative pressure can be maintained at about the Hg lower than atmospheric pressure 25-75mm.The time that the myeloid tissue 7 that negative pressure can be maintained at damage is enough to reduce the edema of spinal cord 7 or controls the spinal fluid seepage.In addition, the myeloid tissue 7 that negative pressure can be maintained at damage is enough to regulate the time of myeloid tissue 7, and the stage reduced to reach recovery from illness and antibacterial numeration for example, can be successfully so that accept Retreatment (lobe (flaps), skin transplantation).Method can be used at least 4 hours, or can use many days.When vacuum-therapy finishes, can remove stitching thread 8 and make skin 2 opening again.Then can remove porous material 10 and again sew up sealing skin 2.

Method also can comprise that the tissue that is placed in above the myeloid tissue 7 of damage by

protective layer

40,50 and

protective layer

40,50 is sealed in to the myeloid tissue 7 that approaches damage keeps negative pressure for the myeloid tissue 7 in damage.The step that

protective layer

40,50 is sealed in to the tissue around the myeloid tissue 7 of damage can comprise by

protective layer

40,50 deadlocked seal and adhere to the tissue around the myeloid tissue 7 of damage.Protective layer 50 can provide from the form of attachment flaps (self-adhesive sheet) 50, and it can be positioned at above the myeloid tissue 7 of damage.In such a case, the step of seal protection layer 50 can comprise by from attachment flaps 50 deadlocked seal and adhere to the tissue around the myeloid tissue 7 of damage, between the tissue around the myeloid tissue 7 of sheet 50 and damage, to form and to seal.In addition, operationally with the form of gas communication, connect vacuum system 30 and can comprise with the step of porous material 10 vacuum valve 42 that is connected vacuum system 30 and protective layer 40.

Embodiment

Spinal Cord Injury in Rats and negative pressure expose

Experiment 1

Implement series of experiments and rat is dampened to the effect of the rear spinal cord of damage to determine negative pressure.In first animal scheme, obtain 250-300 gram Sprague Dawley rat and set up contusion of spinal cord model and confirmation.Produce the method for damaging and estimate recovery and be based on Wrathall etc., the contusion of spinal cord damage of rat: classification, can repeat, the generation of damage group, experimental neurology (Spinal Cord Contusion in the Rat:Production of Graded, Reproducible, Injury Groups, Experimental Neurology 88,108-122 (1985)) description of contusion of spinal cord damage in.The development surgical technic is for the spinal cord that exposes anesthetized rat and lean on body by the circle that falls 10 gram weight through glass tubing from 5cm height and produce consistently and dampen damage.The half rat is untreated matched group, and second half have be exposed to 4 hours negative pressure (lower than atmospheric pressure 25mm Hg) the contusion zone.Yet the degree of damage does not produce remarkable damage (they recover rapidly) in control animal, and therefore can not compare treatment group animal and control animals.

Experiment 2

Set up second scheme, wherein on spinal cord, suffer more serious damage (10 gram weight fall from higher height-7.5cm).28 large (300 gram) Sprague Dawley rats are purchased a period of time and are made it to adapt to the condition of supporting of closing.On operation same day, make animal calm and scrape hair at its back and clean with for operation.Make the midline incision for preparing through spinal column extend and expose darker muscle of back with fascia by skin and subcutaneous tissue and the large flesh of skin (maximus muscle).Be located away from center line paired muscle the offside retraction (retracted laterally) that center line (trapezius muscle and hiding latissimus dorsi m.) is joined.Deep ' posture ' muscle for example is connected to ridge oblique (spinotrapezius) and/or the erector spinae (sacrospinal) itself of spinal bone structure and also retracts at center devision offside.This has exposed spinous process and some hiding transverse process.In the T7-T9 level, remove spinous process between two continuous vertebras and little transversospinales, expose spinal cord surface (dura mater).Implement laminectomy at T-8.Method based on Wrathall etc., make spinal stabilization at T-7 and T-9 and highly fall 10 gram weight to produce moderate spinal cord injury from 7.5cm.5 animals died from respectively its initial operation same day (3 matched group and 2 in the vacuum-therapy group), and 1 animal dead in the early stage matched group of experiment, entered latter 2 days remaining 22 animals of experiment.While finishing to experiment, 11 animals have been randomized to either each group in matched group and 25mm Hg vacuum group.

For control rats, do not provide treatment, and damage is sewn sealing.For vacuum-therapy group rat, polyvinyl alcohol vacuum pack system (Vacuseal Plus, Polymedics, Belgium) is placed on spinal cord and skin is sewn sealing, and vacuum tube passes through incision extension.After within 1 day, postponing, to each animal of vacuum-therapy group, apply lower than the vacuum (negative pressure) of atmospheric pressure 25mm Hg 4 hours.When this time finishes, make animal again calm, remove vacuum pack system, and skin incision is sewed up again with monofilament linea suturalis.

Check cutting part every day.Check that animal self drains the sign of its bladder capacity.Any animal that can not drain is accepted manual auxiliary facilities 3 times with 8 hours intervals every day.Check autophagy metabolism (auto-cannibalism), decubital ulcer and the degree of hydration (squeezing test (pinchtest)) of animal every day.Animal is closed to be supported in soft sized (soft shavings) so that the probability of decubital ulcer development reduces to minimum.Food is placed in the cage bottom so that edible.Animal is checked the recovery of hind leg motor function every day, and each hind leg is adopted to improved Tarlov marking system, and (0=is without motion, without load-bearing; The 1=light exercise, without load-bearing; 2=frequently moves, without load-bearing; The 3=load-bearing, the 1-2 step; The defective walking of 4=; The flawless walking of 5=).Animal is tested (they can no longer can be held and slip down from this plane in this angle) on clinoplain by every day, and checks hind leg grip (grip strength).Animal latter 14 days of operation by euthanasia and remove spinal column and carry out histological examination.

Experimental result provides in table 1 and 2, and " 0 " day is the operation same day.Several animals present minimum damage/defect and during weight falls, enough damages can not be arranged.(

control animal

1,2,11 and treatment group animal 3,9,10.Referring to table 1 and 2).2 animals present serious/damage and not recovery fully.(control animal 5 and treatment group animal 2.Referring to table 1 and 2).Be sure of these remaining whole 7 control animals and 7 treatment group animals there is enough damages but be serious/damage fully.

For the purpose of analyzing, think that animal " recovery " is that it reaches at least 4/4 and scores that day.In 7 control animals, in the time of postoperative 8 days in one's hands, 3 animals do not return at least 4/4 score (right lower limb/left lower limb-defective walking (walking with deficit)).(

animal

3,6,7, table 1).In remaining 4 control animals (

animal

4,8,9,10), 3 animals reached 4/4 at the 4th, 6 and 13 days scores, and 1 animal has reached 4/5 at the 7th day and scores.Therefore, 4 control animals are at average 7.5+/reached at least 4/4 in-3.35 days to score.For the treatment group animal, whole 7 animals (

animal

1,4,5,6,7,8,11) are at average 5.14+/reached at least 4/4 in-1.24 days to score.Therefore, it is evident that the spinal column to damage applies the speed (p=0.059) that 25mm Hg vacuum can increase functional rehabilitation.

table 1. matched group

table 2. vacuum-therapy group

Experiment 3

Formulate the another kind of still scheme of the more serious damage that will cause irrecoverable (permanent) functional defect that wherein produces.Dampen the technology of the employing NYU contusion of spinal cord system of example based on W.M.Keck neuroscience joint study center (Center for Collaborative Neuroscience)-spinal cord injury research project (The Spinal Cord Injury Project) exploitation.These systems (being called at present " MASCIS ") are set up and can pass through the BiologyDepartment at Rutgers University (W.M.Keck neuroscience joint study center (Center for Collaborative Neuroscience) by conventional, Piscataway (Piscataway), New Jersey (New Jersey)) buy.

In above-mentioned experiment, animal is fixed the operation according to body weight, but animal determines according to the age to be performed the operation in this experiment.Long Evans hooded rat was performed the operation so that damage the seriousness standardization when 77 day age.Before operation between 1 and 6 day, some animals are by calm and be transported to the toy MRI imaging mechanism (the SmallAnimal MRI Imaging Facility of Wake Forest University School ofMedicine) of Wake Forest medical college, and adopt Bruker Biospin Horizontal Bore 7Tesla toy scanning device (Etta woods root (Ettlingen), Germany (Germany)) at T9-T10 horizontal sweep spinal cord.Then make the animal be scanned recover in anesthesia in the cage of heating.At the anesthetized animal on the same day of operation, and back part of animal is scraped hair and is adopted depilatory cream.Adopt aseptic technique, in the T9-T10 level, implement laminectomy.Adopt NYU contusion of spinal cord system impacting body (impactor) and use the 10 gram clubs that highly fall from 25mm to clash into spinal cord at T9-T10.The animal of matched group has the otch of the sealing sewed up, and animal is recovered in the cage of heating.For the treatment group animal, polyvinyl alcohol vacuum pack system (VersaFoam, Kinetic Concepts, Inc., San Antonio, TX) is placed on spinal cord, myometrial suture sealing, and apply 25mm Hg vacuum lower than atmospheric pressure 25mm Hg 8 hours.After this time, the treatment group animal, by again calm, is opened otch, removes vacuum pack system and again sews up sealing cut.If the animals received Postoperative MRI, animal is scanned 8 hours after shock.

Functional rehabilitation is marked with BBB, from 22 comments minute of W.M.Keck neuroscience joint study center (Center for Collaborative Neuroscience), is estimated.(table 3).Monitored 21 days of animal, then through being exposed to the CO of lethal dose<sub TranNum="165">2</sub>make euthanasia.Bladder is pushed by every day and the sign of the monitored autophagy metabolism of animal, decubital ulcer, skin lesion etc.Remove and anyly present the animal of autophagy metabolism sign and make euthanasia in research.Decubital ulcer and skin lesion are when appropriate and seek advice from ARP veterinary work personnel and treated.Although this nursing is arranged, in the process of this experiment, some animal deads, and other animal is because other problem is left out.<tables TranNum="166" num="0001"> <table TranNum="167"> <tgroup TranNum="168" cols="1"> <colspec TranNum = "169" colname = "c001" colwidth = "100 % "/> <tbody TranNum="170"> <row TranNum="171"> <entry TranNum="172" morerows="1">, value ,,,, ,,,, ,,,, , condition, , 0, , , there is no observable hind limb movement , , 1,, , slight movement of one or two joints , usually the hip & / or knee, , 2, , , a stretching of a joint or joints stretching exercises with a slight movement of the other joints , 3, , , stretching two joints ,, 4,,, HL slight movement of all three joints , , 5, , , slight movement of two joints and a third joints stretching exercises , , 6, , , stretching two joints and slight movement of the third joint , 7 , all three joints of stretching exercises HL , , 8, , , no weight support paw foot wing song (Sweeping) or no weight support paw foot flat (Plantar,,,,,, placement),, 9,,, only in the standing posture ( that is, when at rest ) has to support the weight of the flat or occasionally , when </ entry> </ row> </ tbody> </ tgroup> </ table> </ tables> <tables TranNum="173" num="0002"> <table TranNum="174"> < tgroup TranNum = "175" cols = "1"> <colspec TranNum="176" colname="c001" colwidth="100%"/> <tbody TranNum="177"> <row TranNum="178"> <entry TranNum = "179" morerows = "1">,,,,, often or consistently support the weight of the back foot stride and non- stride , 10 , and occasionally support the weight of the foot ; non forelimb (FL) - HL coordination , 11, often to support the weight of consistent plantar stepping and non- FL-HL coordination , 12, often to support the weight of consistent plantar stepping and occasional FL-HL coordination , 13 , often to support consistent plantar stepping weight and often the FL-HL coordination , 14, when it is initially in contact with the surface , and just before the end of the standing posture of the foot from the ground or from time to time ,,,, , at the end when stepping , consistent weight supported plantar stepping , consistent FL-HL coordination and , ,,,, during the movement of the main paw position (pawposition) for the rotation ( inward or outward ) ; always If a ,,,, , the FL-HL coordination ; and occasional dorsal stepping , 15 , consistent plantar stepping and consistent FL-HL coordination ; and no forward movement during limb ,,,, , toe clearance (Toe, clearance) or occasional toe clearance ; major paw position and initial contact , ,,,, body parallel , 16, during a foot stepping gait and always consistent as one of the FL-HL coordination ; and body forward ,,,, , frequent toe clearance during exercise ; major paw position parallel to and at the time from initial contact , ,,,, earth rotation , and 17 , in consistently stepped foot during gait and consistent FL-HL coordination ; and body forward ,,,, , frequent toe clearance during exercise ; major paw position at initial contact and when the flat ground , ,,,, line , and 18 during the gait consistent plantar stepping and consistent FL-HL coordination ; and body forward ,,,, , consistent toe clearance occurs during exercise ; main the position of the feet flat during initial contact ,,,, , and from the ground when the line rotation , 19, during gait consistent plantar stepping and consistent FL-HL coordination ; and body forward , ,,,, consistently occurs during movement toe clearance ; major paw position at initial contact and leave, ,,,, while in parallel ; and tail down in some or all of the time , and 20 , consistent consistent plantar stepping and coordinated gait ; consistent toe clearance ; Lord, ,,,, paw position is parallel to the ground when the initial contact and ; and trunk instability ; tail always ,,, , , like a ground up , 21, consistent plantar stepping and consistent coordination of gait ; consistent toe clearance ; Lord, ,,,, paw position to standing posture for the entire period in parallel ; trunk stability consistent ; tail, ,,,, Department consistently upward </ entry> </ row> </ tbody> </ tgroup> </ table> </ tables> table 3.BBB movement rating scale

For these researchs of permanent damage, 36 rats with complete dura mater complete research analyzed.The animal of 11 (11) vacuum-therapy that begin one's study, due to urinary tract infection and renal failure, 1 animal was removed with 1 animal and removes 8 weeks the time in the time of 5 weeks.Therefore, the animal of 9 vacuum-therapy completes the research of 12 weeks.27 control animals start and complete research.The animal of vacuum-therapy presents larger functional rehabilitation rate (p<0.072) 3 weeks the time after damage: BBB scoring=12.818+/-1.401 (n=11) vacuum-therapy group is to 11.704+/-2.391 (n=27) matched group.The animal of vacuum-therapy presents significantly larger functional rehabilitation rate (p<0.001) 4 weeks the time after damage: BBB scoring=13.625+/-1.303 (n=11) vacuum-therapy group is to 11.500+/-0.707 matched group (n=27).Fig. 6 and 7.The recovery rate of vacuum-therapy animal is stable level, and the recovery level of control animals moves closer to the level of vacuum-therapy animal.Fig. 6 and 7.(note, studied 3 weeks of some animals (usually early stage in research), and the observed functional rehabilitation of some animals 12 weeks).

Except BBB estimates, adopt this is tested to method listed above, 2 sectional areas with the analyzed damage of animal MRI scanning front and rear spinal cord of complete dura mater change (for example, with mm ²mean) (scanning after the animal of vacuum-therapy is implemented to damage after treatment).In carrying out 4 animals of this analysis, only have the animal of 1 vacuum-therapy do not there is any technology or clash into error and can be used.In control animal, 1 has less height error, and its pin (release pin) of deviating from the contusion of spinal cord system closes when leave behind in foster place and occurs from it; All other control animals have significant shock error, and it hinders the analysis of spinal cord sectional area.The height that Machine Records falls the rat weight of vacuum-therapy is 24.8mm, and is 25.782mm for the height of control rats.

Forward Fig. 8 to, when scanning is carried out along spinal column (to afterbody), control animals shows that sectional area increases a little.To clashing into front scanning and clashing into rear scanning, both are apparent for this.More than damage, with the following position of damage, sectional area scans and clashes between rear scanning not remarkable different before shock.Before the above shock of damage, meansigma methods is 5.49mm ²+/-0.2 (n=5) is to clashing into rear meansigma methods 5.32mm ²+/-0.23 (n=4): p<0.211) (before the following shock of damage, meansigma methods is 6.81mm ²+/-0.25 (n=3) is to clashing into rear meansigma methods 6.46mm ²+/-0.78 (n=4): p<0.464).Yet, in impact site, significantly be greater than (p<0.001) shock starting section for sectional area after the control animals shock long-pending: clash into front area average 5.63mm ²+/-0.24 (n=5 scanning) is to area 6.43mm after average shock ²+/-0.32 (n=4 scanning).This most likely causes spinal cord swelling due to the restriction because of dura mater, because the bone that will become spinal cord diameter limiting factor is removed.

Do not resemble control animals, the animal of vacuum-therapy does not show that after vacuum-therapy the average diameter of damage location spinal cord increases, Fig. 9.Before the average shock of level of damage, area is 7.28mm ²+/-0.73 (n=4 scanning) is to area 7.03mm after average shock ²+/-0.99 (n=4 scanning) (p<0.73).The similarity of spinal cord size before damage location clashes into and after treatment is most likely owing to removing fluid in dura mater, so spinal cord keeps initial diameter.

Before the above area of damage clashes into, with scanning after treatment, be similar (there is no significant difference).Before shock, the above area of damage is that 7.79+/-0.64 (n=3 scanning) is to treating rear area 8.33+/-1.11 (n=5 scanning) (p<0.48).Below animal injury for vacuum-therapy, scan, after treatment, the sectional area of spinal cord significantly is greater than the sectional area before clashing into: clash into front area 7.61+/-0.43 (n=4 scanning) to treating rear area 10.76+/-0.35 (n=4 scanning), p<0.001.To the possible explanation that damages following spinal cord sectional area and increase, may be to be attributable to venous congestion.Perhaps, the vacuum applied may, automatically from the cerebrospinal fluid of spinal cord absorption on every side, make spinal cord expand to fill the canalis spinalis area in vertebral body.This expansion will play a part to make the dura mater internal pressure to reduce to minimum and contribute to the Cell protection vigor.

Those skilled in the art will be expressly understood these and other advantage of the present invention in above description.Therefore, those skilled in the art will appreciate that and can make and change or improve and do not deviate from extensive invention theory of the present invention embodiment described above.Therefore should be appreciated that and the invention is not restricted to specific embodiments described here, and be intended to comprise all changes and improvement, in the scope and spirit of the present invention that these changes and improvements are set forth in the claims.

Claims

1. a device that is used for the treatment of the myeloid tissue of damage, it comprises:

But multiporous biological bond material, but this material has the pore structure that is shaped to allow gas communication between one or more holes of multiporous biological bond material and the myeloid tissue for the treatment of, but but the selected surface of multiporous biological bond material that the multiporous biological bond material is at least placed in the myeloid tissue of contiguous damage has enough little hole to prevent from being organized in wherein, grows; With

For generation of the vacuum source of negative pressure, but its in the mode with multiporous biological bond material gas communication to myeloid tissue's distribution negative pressure of being treated.

2. according to the device of claim 1, but wherein the multiporous biological bond material comprises out the chamber collagen protein.

3. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises polyglycols citron acid esters.

4. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises polyglycols citron acid esters and collagen protein.

5. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises elastin laminin, hyaluronic acid, alginate or its combination.

6. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises the electrospinning material.

7. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises cast-molding material.

8. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises printing material.

9. according to the device of claim 1 or 2 claim, but but the selected surface of multiporous biological bond material that wherein the multiporous biological bond material is at least placed in the myeloid tissue to contiguous damage has the pore size that is less than fibroblast and cord cell size.

10. according to the device of claim 1 or 2, but but wherein the multiporous biological bond material has the pore size that is greater than fibroblast and cord cell in the inside of biology bond material.

11. according to the device of claim 1 or 2, but but the position the selected surface of multiporous biological bond material that wherein the multiporous biological bond material is placed in the myeloid tissue except contiguous damage has the pore size that is greater than fibroblast and cord cell.

12. according to the device of claim 1 or 2 claim, but the protein motion that wherein pore size of multiporous biological bond material passes through even as big as allowing the large I of albumin.

13. according to the device of claim 1 or 2, but wherein the multiporous biological bond material comprises at least one sealed surface to prevent that negative pressure from therefrom transmitting.

14. according to the device of claim 1 or 2, but but the pore size that forms granulation tissue is impelled on the surface the surface of the selection that wherein the multiporous biological bond material comprises the multiporous biological bond material of placing even as big as the myeloid tissue except contiguous damage.

15., according to the device of claim 1 or 2, wherein vacuum source comprises vacuum pump.

16., according to the device of claim 1 or 2, its protective layer that comprises the myeloid tissue that is shaped to the covering damage is to keep negative pressure under the protective layer at the Spinal Cord tissue.

17., according to the device of claim 16, wherein protective layer comprises self attachment flaps.